Circular RNA CEP128 promotes bladder cancer progression by regulating Mir‐145‐5p/Myd88 via MAPK signaling pathway

Abstract

The present experiment was designed for exploring the regulatory mechanism of circ‐CEP128/miR‐145‐5p/MYD88 axis in bladder cancer. MiRNAs and circRNAs expression data were derived from Gene Expression Omnibus database with bladder tumor tissues and paracarcinoma tissue samples. Differentially expressed genes in tumor were analyzed via R software. Interaction network of differently expressed miRNAs and differently expressed mRNA was established by means of Cytoscape software. CircCEP128 and miR‐145‐5p expression levels were determined using qRT‐PCR. The expression of MAPK signaling‐related proteins MYD88, p38, ERK and JNK was examined by western blot. The relationship between circCEP128 and miR‐145‐5p was validated using RNA immunoprecipitation. The level of cell propagation and migration was determined by CCK8 and wound healing assay, 5‐bromo‐2′‐deoxyuridine assay and migration assay. Cell apoptosis rate and cell cycle were detected via flow cytometry. Tumor xenograft assay was implemented to investigate the function of circCEP128 in vivo. CircCEP128 and MYD88 were overexpressed in bladder cancer based on microarray analysis and miR‐145‐5p was a potential targeting factor in bladder cancer. CircCEP128 targeted miR‐145‐5p and miR‐145‐5p targeted MYD88. Expression of miR‐145‐5p was decreased in cancer samples. Knockdown of circCEP128 induced the inhibition of cell viability and mobility and cell cycle arrest. Overexpression of miR‐145‐5p or knockdown of circCEP128 promoted MAKP signaling pathway and related proteins expression. In addition, knockdown of circCEP128 suppressed the growth of bladder cancer tumor tissues in vivo. Overexpression of circCEP128 promoted bladder cancer progression through modulating miR‐145‐5p and MYD88 via MAKP signaling pathway.

circRIP2 accelerates bladder cancer progression via miR-1305/Tgf-β2/smad3 pathway

“…Hence, researches of circular RNAs are divided into 2 parts, one is to identify its carcinogenic role, the other is to prove its application as a biomarker [5]. Serving as an oncogene or tumor suppressor gene, in bladder cancer, ciRS-7 is found to suppress bladder cancer growth by elevating p21 [6]; hypoxia elevates circELP3 to promote bladder cancer progression and drug resistance [7]; circular RNA CEP128 promotes bladder cancer cell propagation and migration via regulating MAPK signaling [8]; and circHIPK3 decreases lung metastasis through suppressing heparanase expression [9]. Besides, as a biomarker [10], up-regulated circPRMT5 in the exosomes from serum and urine positively correlates with metastasis of bladder cancer patients [11].…”

Downregulated hsa_circ_0077837 and hsa_circ_0004826, facilitate bladder cancer progression and predict poor prognosis for bladder cancer patients

“…To further explore the roles of these all DE‐circRNAs on downstream genes, GO enrichment, KEGG pathway analysis were also conducted to evaluate the predicted critical genes of them. As shown in Figure 3B,C, several cancer‐related pathways, such as pathways in cancer, cell cycle, PI3K‐Akt signaling pathway, MAPK signaling pathway, cellular senescence, were significantly enriched and promote various cancer cell growth, invasion, and metastasis 56,64,65 . Furthermore, protein‐protein interaction (PPI) network and module analysis of 94 DE‐genes predicted by screened eight DE circRNAs are delineated in Figure 6.…”

CircDUSP16 promotes the tumorigenesis and invasion of gastric cancer by sponging miR-145-5p

“…Mechanistically, circRNA can sponge miRNA to participate in the progression of GC [11,13]. Previous studies showed that circZNF609, circ_0058063, and circCEP128 sponge miR-145-5p to promote cancer progression [26][27][28]. Likewise, we identified that circDUSP16 was co-localized with miR-145-5p in the cytoplasm of GC cells, and displayed a negative correlation with miR-145-5p expression in GC tissue samples.…”